Ischemia and reperfusion can cause significant injury of skeletal muscle, which is a vulnerable tissue in the extremities. Trauma, autogenous skeletal muscle transplantation, surgical incision, vascular clamp application during vascular surgery or musculoskeletal reconstructive surgery, and sustained strenuous exertion can also induce skeletal muscle damage with deleterious systemic consequences. Protection of skeletal muscle from ischemia and reperfusion injury is therefore an important therapeutic goal. Although various measures including a tissue-preserving solution and cold immersion are used to preserve intact organs and skeletal muscle, a more effective method or pharmacological agents to protect skeletal muscle from ischemia/reperfusion injury is needed.
In addition, exercise, particularly strenuous exercise, can result in skeletal muscle injury. Skeletal muscle injury can result from over-activity and/or overload of the muscles and can result in impaired muscle function. At the present time, there is no effective pharmacological therapy that can protect the skeletal muscle from exertion-related injury. In addition, in subjects with degenerative muscle disease, there has not been an effective drug therapy that can ameliorate skeletal muscle injury. Thus, there is a need for methods and agents suitable for the treatment of skeletal muscle injury resulting from exercise.